Distinct Structures and Dynamics of Chromatosomes with Different Human Linker Histone Isoforms

Mol Cell. 2021 Jan 7;81(1):166-182.e6. doi: 10.1016/j.molcel.2020.10.038. Epub 2020 Nov 24.


The repeating structural unit of metazoan chromatin is the chromatosome, a nucleosome bound to a linker histone, H1. There are 11 human H1 isoforms with diverse cellular functions, but how they interact with the nucleosome remains elusive. Here, we determined the cryoelectron microscopy (cryo-EM) structures of chromatosomes containing 197 bp DNA and three different human H1 isoforms, respectively. The globular domains of all three H1 isoforms bound to the nucleosome dyad. However, the flanking/linker DNAs displayed substantial distinct dynamic conformations. Nuclear magnetic resonance (NMR) and H1 tail-swapping cryo-EM experiments revealed that the C-terminal tails of the H1 isoforms mainly controlled the flanking DNA orientations. We also observed partial ordering of the core histone H2A C-terminal and H3 N-terminal tails in the chromatosomes. Our results provide insights into the structures and dynamics of the chromatosomes and have implications for the structure and function of chromatin.

Keywords: Cryo-EM; NMR; chromatin structure; chromatosome; chromatosome dynamics; chromatosome structure; linker histone isoform; linker histone tail; nucleosome; single-chain antibody.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • DNA / chemistry*
  • DNA / ultrastructure
  • Histones / chemistry*
  • Humans
  • Nucleosomes / chemistry*
  • Nucleosomes / ultrastructure
  • Protein Isoforms / chemistry


  • Histones
  • Nucleosomes
  • Protein Isoforms
  • DNA